Endocrine Abstracts

The protection of genetic integrity and establishment and maintenance of correct epigenetic marks are crucial in the germ line to prevent transmission of harmful information to next generations. Male germ cell differentiation is governed by accurate, spatially and temporally controlled gene expression patterns. Male germ cells produce several classes of small non-coding RNAs that are known to regulate gene expression at both post-transcriptional and transcriptional level. These include Dicer-dependent microRNAs (miRNAs) and endogenous small interfering RNAs (endo-siRNAs), and Dicer-independent piwi-interacting RNAs (piRNAs). The functions of these small RNAs in male germ cell-specific gene regulation are still largely unclear. The goal of our research is to clarify the roles of small non-coding RNAs and the mechanisms of post-transcriptional gene control during male germ cell differentiation. We have shown that Dicer is required for spermatogenesis by using a knockout mouse model with Dicer1 deletion specifically in post-natal male germ cells. Our results demonstrate that Dicer and Dicer-dependent small RNAs are crucial for the correct nuclear polarization and chromatin condensation of developing spermatids. piRNAs that are expressed predominantly in the germ line, form a big, complex and functionally diverse group of small RNAs. piRNA expression is known to be greatly induced in late meiotic cells and round spermatids, and interestingly, we have demonstrated that in these cells, piRNAs accumulate in an intriguing cytoplasmic granule, a chromatoid body (CB). We have isolated CBs from mouse testis and characterized its molecular composition to better understand the role of the CB in the post-transcriptional RNA regulation in haploid cells. These pathways appear to be essential for normal spermatogenesis in mouse, thus highlighting their significance in maintaining male fertility.